Myelodysplastic Syndromes Staging 

Updated: Oct 18, 2019
  • Author: Matthew C Foster, MD; Chief Editor: Emmanuel C Besa, MD  more...
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WHO Classification and IPSS of Myelodysplastic Syndromes

The 2016 World Health Organization (WHO) classification of myelodysplastic syndromes (MDS), [1] as well as the International Prognostic Scoring System (IPSS), are provided below. [2]  The 2016 classification replaced terms such as refractory anemia and refractory cytopenia with MDS and added a provisional entity, refractory cytopenia of childhood.

Myelodysplastic syndromes are a group of clonal myeloid neoplasms characterized by ineffective hematopoiesis that present clinically as cytopenia(s), dysplasia in one or more hematopoietic cell lines in the bone marrow, and risk of transformation to acute myeloid leukemia (AML). [3]

See Myelodysplastic Syndromes: Classification, Features, Diagnosis, and Treatment Options, a Critical Images slideshow, to help identify, classify, work up, and treat these disorders.

Evidence of clonality may support the diagnosis of MDS and may manifest as an increase in bone marrow myeloblasts or recurrent cytogenetic abnormalities, although these findings are not necessary to fulfill the diagnostic criteria.

Myelodysplastic syndromes appear to represent several molecularly unique entities whose variation makes constructing a concise and practical framework difficult.

WHO classification of MDS

The WHO classification system of MDS relies on incorporating clinical features, peripheral blood and bone marrow findings, and cytogenetic analysis. [1] This classification also includes a collection of heterogeneous neoplasms that share features of MDS and myeloproliferative neoplasms.

These "overlap syndromes" fall under the classification "myelodysplastic/myeloproliferative neoplasms" (MDS/MPN) and include the following:

  • Chronic myelomonocytic leukemia (CMML-1 and CMML-2)
  • Atypical chronic myeloid leukemia (aCML), BCR-ABL1 negative
  • Juvenile myelomonocytic leukemia (JMML)
  • MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)
  • MDS/MPN, unclassifiable

Although a detailed discussion of the overlap disorders is beyond the scope of this review, they share clinical, pathologic, and therapeutic features with MDS and can be treated similarly when they present with more features of MDS than MPN.

The WHO MDS classification comprises the following:

  • MDS with single-lineage dysplasia
  • MDS with ring sideroblasts (MDS-RS):
  • MDS-RS and single-lineage dysplasia
  • MDS-RS and multilineage dysplasia
  • MDS with multilineage dysplasia:
  • MDS with excess blasts–1 (MDS-EB–1)
  • MDS with excess blasts–2 (MDS-EB–2)
  • MDS associated with isolated del(5q)
  • MDS, unclassifiable (MDS-U)
  • Refractory cytopenia of childhood
  • Myeloid neoplasms with germ line predisposition 
  • Therapy-related MDS (t-MDS)

See Table 1, below.

Table 1. World Health Organization criteria for myelodysplastic syndromes (Open Table in a new window)

Syndrome

Dysplastic lineages 

Cytopenias* 

Ring sideroblasts as % of marrow erythroid elements 

Bone marrow (BM) and peripheral blood (PB) blasts 

Cytogenetics by conventional karyotype analysis 

MDS with single lineage dysplasia (MDS-SLD) 

1 or 2 

< 15%/< 5%† 

BM < 5%

PB < 1%, no Auer rods 

Any, unless fulfills all criteria for MDS with isolated del(5q) 

MDS with multilineage dysplasia (MDS-MLD) 

2 or 3 

1-3 

< 15%/< 5%† 

BM < 5%

PB < 1%, no Auer rods 

Any, unless fulfills all criteria for MDS with isolated del(5q) 

 MDS with ring sideroblasts (MDS-RS) with single lineage dysplasia (MDS-RS-SLD) 

1 or 2 

≥15%/≥5%† 

BM < 5%

PB < 1%, no Auer rods 

Any, unless fulfills all criteria for MDS with isolated del(5q) 

MDS-RS with multilineage dysplasia (MDS-RS-MLD) 

2 or 3 

1-3 

≥15%/≥5%† 

BM < 5%

PB < 1%, no Auer rods 

Any, unless fulfills all criteria for MDS with isolated del(5q) 

MDS with isolated del(5q) 

1-3 

1-2 

None or any 

BM < 5 %

 PB < 1%, no Auer rods 

del(5q) alone or with 1 additional abnormality except −7 or del(7q)

MDS with excess blasts– 1 (MDS-EB-1)

0-3 

1-3 

None or any 

BM 5%-9% or

PB 2%-4%, no Auer rods 

Any 

MDS-EB-2 

0-3 

1-3 

None or any 

BM 10%-19% or

PB 5%-19% or Auer rods 

Any 

MDS, unclassifiable (MDS-U) with 1% blood blasts 

1-3 

1-3 

None or any 

BM < 5%

 PB = 1%,‡ no Auer rods 

Any 

MDS-U with single lineage dysplasia and pancytopenia 

None or any 

BM < 5%

PB < 1%, no Auer rods

Any 

MDS-U based on defining cytogenetic abnormality

1-3 

< 15%§ 

BM < 5%

PB < 1%, no Auer rods 

MDS-defining abnormality 

Refractory cytopenia of childhood 

1-3 

1-3 

None 

BM < 5%

PB < 2% 

Any 

*Cytopenias are defined as: hemoglobin, < 10 g/dL; platelet count, < 100 × 109/L; and absolute neutrophil count, < 1.8 × 109/L. Rarely, MDS may present with mild anemia or thrombocytopenia above these levels. PB monocytes must be < 1 × 109/L

† If SF3B1 mutation is present.

‡ 1% PB blasts must be recorded on at least 2 separate occasions.

Patients with therapy-related MDS have blood and bone marrow findings of one of the above diagnostic categories (frequently with multilineage dysplasia) and a past history of exposure to cytotoxic chemotherapy and/or radiation therapy administered for treatment of cancer or nonneoplastic disease. Erythroid precursors comprise ≥50% of bone marrow nucleated cells. A number of  these patients been shown to have germ line mutations in cancer susceptibility genes; so a careful family history is warranted.

Myeloid neoplasms with germ line predisposition are classified as follows:

  • No preexisting disorder or organ dysfunction - germ line  DDX41 mutation
  • Preexisting platelet disorder - germ line  RUNX1ANKRD26, or  ETV6 mutation
  • Other organ dysfunction - germ line GATA2 mutation; associated bone marrow failure syndromes, telomere biology disorders, or Down syndrome

IPSS and Revised IPSS (IPSS-R)

Although several prognostic scoring systems have been developed, [4, 5] the most widely used has been the IPSS. [2] The IPSS-R is a recdent revision of the IPSS that refines cytogenetic prognostic categorization and weights the prognostic score according to the severity of cytopenias in addition to the bone marrow blast percentage. The sum of the assigned points yields a prognostic score, which defines survival and risk of progression to AML. In addition to the clinical and pathologic variables included in the IPSS-R, point mutations in genes such as TP53, EZH2, ETV6, RUNX1, and ASXL1 have been shown to identify patients at risk for shortened survival or transformation to acute leukemia. [6] See the tables below.

Table 2. IPSS-R assignment of score (Open Table in a new window)

 

Score Value

Prognostic variable

0

0.5

1

1.5

2

3

4

Marrow blasts (%)

< 2

-

2 - < 5

-

5-10

>10

-

Karyotype

Very Good

-

Good

Intermediate

Poor

Very Poor

Hemoglobin (g/dL)

≥10

-

8 - < 10

< 8

-

-

-

Absolute Neutrophil Count (x 109/L)

≥0.8

< 0.8

-

-

-

-

-

Platelet Count (x 109/L)

≥100

50 - < 100

< 50

-

-

-

-

Very Good Karyotype: del(11q), -Y; Good karyotype: 46XX, 46XY, del(5q), del(20q); poor karyotype: complex (≥3 unrelated abnormalities) or chromosome 7 abnormalities; intermediate karyotype: karyotypes not defined as good or poor.

 

 

 

Table 3. IPSS-R risk groups, by sum of score [7] (Open Table in a new window)

Risk Category

(% IPSS-R population)

Overall Score

Median Survival (years)

Time for 25% of patients to progress to AML

Very Low (19)

≤1.5

8.8

Not reached

Low (38)

2-3

5.3

10.8

Intermediate (20)

3.5-4.5

3.0

3.2

High (13)

5-6

1.6

1.4

Very High (10)

>6

0.8

0.73

AML = acute myeloid leukemia; IPSS-R = Revised International Prognostic Scoring System.